Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives.

OBJECTIVE: To estimate the relative risk of recurrence of oral cleft in first degree relatives in relation to cleft morphology.

DESIGN: Population based cohort study.

SETTING: Data from the medical birth registry of Norway linked with clinical data on virtually all cleft patients treated in Norway over a 35 year period.

PARTICIPANTS: 2.1 million children born in Norway between 1967 and 2001, 4138 of whom were treated for an oral cleft.

MAIN OUTCOME MEASURE: Relative risk of recurrence of isolated clefts from parent to child and between full siblings, for anatomic subgroups of clefts.

RESULTS: Among first degree relatives, the relative risk of recurrence of cleft was 32 (95% confidence interval 24.6 to 40.3) for any cleft lip and 56 (37.2 to 84.8) for cleft palate only (P difference=0.02). The risk of clefts among children of affected mothers and affected fathers was similar. Risks of recurrence were also similar for parent-offspring and sibling-sibling pairs. The "crossover" risk between any cleft lip and cleft palate only was 3.0 (1.3 to 6.7). The severity of the primary case was unrelated to the risk of recurrence.

CONCLUSIONS: The stronger family recurrence of cleft palate only suggests a larger genetic component for cleft palate only than for any cleft lip. The weaker risk of crossover between the two types of cleft indicates relatively distinct causes. The similarity of mother-offspring, father-offspring, and sibling-sibling risks is consistent with genetic risk that works chiefly through fetal genes. Anatomical severity does not affect the recurrence risk in first degree relatives, which argues against a multifactorial threshold model of causation.